1'-Cyano Intermediate Enables Rapid and Stereoretentive Access to 1'-Modified Remdesivir Nucleosides.

While biochemical, structural, and computational studies have shown the importance of remdesivir's C1'-substituent in its perturbation of SARS-CoV-2 RdRp action, we recognized the paucity of methods to stereoselectively install substituents at this position as an obstacle to rigorous explorations of SAR and mechanism. We report the utilization of an anomerically pure 1'-cyano intermediate as an entry point to a chemically diverse set of substitutions, allowing for 1'diversification while obviating the need for the tedious separation of anomeric mixtures.